The film was released theatrically in the United States and United Kingdom on March 10, 2006. It earned $15.5 million in its opening weekend in the U.S.,[1] where it was originally rated NC-17 for strong gruesome violence, but was later edited down to an R-rating. An unrated DVD version was released on June 20, 2006. A sequel, The Hills Have Eyes 2, was released in theaters March 23, 2007.

In the New Mexico desert, they encounter a gas station attendant named Jeb (Tom Bower), who tells them of a short-cut through the hills. Taking the supposed short-cut, their tires are punctured by a hidden spike strip. Doug and Bob go look for help, while the rest of the family stays behind. Bobby chases a panicked Beauty into the hills and finds her mutilated body; frightened, he runs and falls, knocking himself unconscious. A young female mutant named Ruby (Laura Ortiz) finds him and protects him from her brother Goggle (Ezra Buzzington). Bob goes back to the gas station for help, and upon investigation he finds news clippings detailing various disappearances that have occurred in the area. He realizes that the attendant purposefully led them to danger by suggesting they take an alternative route through the hills. When Bob exits he finds the hysterical Jeb, who commits suicide in front of him. In fear, Bob attempts to flee, but is attacked by the mutant leader, Papa Jupiter (Billy Drago), and dragged into the mining caves by Jupiter, Jupiter's eldest son Lizard (Robert Joy), and Pluto.

Bobby returns to the trailer, but doesn't mention Beauty's death not wanting to frighten the rest of the family. Later that night, the family is awakened by Bob's screams, and they all rush from the trailer, except for Brenda and the baby, who are left behind. Outside they find Bob being burned alive on a stake and frantically try to save him, but to no avail. Meanwhile, Pluto and Lizard use the distraction to ransack the trailer, where Lizard beats and rapes Brenda. When Lynn returns to the trailer she is greeted by Lizard and Pluto, and forced to let Lizard drink from her breasts while her baby is held at gunpoint. When Ethel returns she is shot by Lizard, and Lynn stabs Lizard in the leg, prompting him to shoot Lynn in the head. Lizard and Pluto flee with the baby after Lizard attempts to shoot Brenda.

Doug and Bobby return to the trailer and discover Lynn and Ethel, who die shortly afterward. Goggle, who is watching the Carters with a pair of binoculars, is attacked by Beast, who tears his throat out, killing him. The next morning, Doug and Beast set off to rescue Catherine. Doug finds an abandoned nuclear testing village, and is knocked unconscious by Big Mama (Ivana Turchetto) during his search. Upon awakening, he escapes an ice box filled with human body parts and continues his search, only to encounter Big Brain (Desmond Askew). After Big Brain tells him the mutants' origins, Doug is attacked by Pluto, who severs two of his fingers with an axe. Pluto almost kills Doug, but Doug manages to gain the upper hand while Pluto is distracted, and kills him with his own axe.

Outside, Doug kills the mutant Cyst (Gregory Nicotero) and continues to search for Catherine. After ordering Lizard to kill Catherine, Big Brain is mauled to death by Beast. Lizard takes a cleaver and prepares to kill Catherine, but finds that Ruby has taken her. Doug sees Ruby running through the hills with Catherine and follows her. At the trailer, Brenda and Bobby prepare an explosive trap, which destroys the trailer, apparently killing Papa Jupiter.

Doug catches up with Ruby, but as she is about to return Catherine, Lizard suddenly attacks him. Lizard and Doug fight, and Lizard is presumed dead. When Doug turns his back Lizard aims a shotgun at him, but Ruby tackles Lizard off a cliff, killing them both. Bobby and Brenda find that Papa Jupiter managed to survive their trap, and Brenda finishes him off. They are then reunited with Doug, Catherine and Beast. As they celebrate their apparent victory, an unknown mutant watches through binoculars from the hills.

Wes Craven, director and writer of the original film, considered a remake after he saw the success of other horror remakes such as The Texas Chainsaw Massacre and The Amityville Horror. The search then began for filmmakers to helm the project. Marianne Maddalena, Craven's long time producing partner, came across Alexandre Aja and his art director/collaborator Grégory Levasseur who had previously made the French slasher film Haute Tension. After showing the film to Craven and the rest of the production crew, they were impressed with the pair. Craven comments that they "demonstrated a multi-faceted understanding of what is profoundly terrifying" and "After viewing the film and then meeting the film makers, I knew I wanted to work with them."[2] Aja and Levasseur then began to re-write the story in what is the pair's first American production.

The film is set in New Mexico, and strongly implies that a large number of atmospheric nuclear weapon tests were performed in that state. In fact, the only atmospheric nuclear detonation in New Mexico was the Trinity test, the first test of a nuclear device conducted on July 16, 1945. The United States carried out most of its atmospheric nuclear weapons tests at the Nevada Test Site and in the Marshall Islands at the lagoons of Bikini and Eniwetok, between 1946 and 1962. The theatrical poster shows Vinessa Shaw's character lying down with a mutant hand on her face.

Prior to filming, Aja and Levasseur had already conceived an idea for the mutants' appearance. "We based all our descriptions and directions on real documents, pictures and footage that we found on the effects of nuclear fallout in Chernobyl and Hiroshima", explains Aja. The Hills Have Eyes utilized the K.N.B. EFX Group Inc. who had done previous work on films such as The Chronicles of Narnia (for which an Academy Award was nominated) and Sin City.

K.N.B. spent over six months designing the mutants, first using 3D designer tools, such as ZBrush, allowing them to use a computer to generate their sculptures. After prosthetics were made, they could be fitted to the actors before filming. Robert Joy, who plays the mutant Lizard, explained, "Every day, these amazing artists took more than three hours to transform me into something that could only be found in a nightmare."[2]

K.N.B. artist Gregory Nicotero was also made a cameo as Cyst, the mutant with the halo head-gear.

Jamison Goei and his team, who had done previous work on Hellraiser: Hellseeker and Halloween: Resurrection, had done over 130 visual effects for the film. A large part of that was digitally constructing the testing village, which in actuality was only one built street with others digitally added. The team also warped the mutant's faces slightly, which is shown mostly in the character of Ruby.

Papa Jupiter displays no deformities. However, as shown in "The Making Of", Papa Jupiter appears to have a large parasitic twin attached to his upper left torso. The young children of the film had their deformities added by CGI, with the exception of Ruby, who had a combination of CGI and makeup.

The casting process began with the selection of The Silence of the Lambs‍ '​s Ted Levine as the character Big Bob. Levine was also a fan of the film Haute Tension. Afterwards, Kathleen Quinlan was cast as Ethel in her first role starring in a horror film (despite appearing in Twilight Zone: The Movie and Event Horizon). Next, Aaron Stanford was cast as Doug Bukowski who "undergoes the most radical transformation of anyone in the Carter family"[2] Stanford even asked not to see any of the mutants in make-up before his character's battle in the testing village so, that way, he'd be truly frightened. When casting Lynn, Doug's wife, Aja wanted to cast Vinessa Shaw whom he had wanted to work with since seeing her in Stanley Kubrick's 1999 film Eyes Wide Shut. Shaw was hesitant to play the role, but after watching Haute Tension, she agreed, explaining: "There was such an odd combination of beauty and terror, it felt almost like an art film. So, after meeting with Alex and Greg, I decided to do it."[2] For the role of Brenda, the filmmakers sought a young actress who had relatively little exposure and found it in Emilie de Ravin who was beginning her rise in the television series Lost. After de Ravin, Dan Byrd was cast as Bobby. Byrd had previous genre experience starring in Salem's Lot.

Aja then had the six actors arrive in the filming location of Morocco early to bond together.

When casting for the mutants, associate producer Cody Zwieg explained: "We needed to find actors who could not only perform the stunt work, handle the extensive makeup and perform in that makeup, but who truly could embody the fierce, primal nature of the mutants' way of life."[2] To play the role of Pluto, Aja looked to Michael Bailey Smith, who had been in A Nightmare on Elm Street 5: The Dream Child. For Lizard, the filmmakers cast Robert Joy, who had made previous genre films such as Amityville 3-D and George A. Romero's Land of the Dead. Ezra Buzzington, impressed with the filmmakers, agreed to play the role of Goggle and even watched a documentary about human cultures engaging in cannibalism. To play the mutant leader, Billy Drago was cast. Drago had previously had a role in Brian De Palma's The Untouchables and other horror features. The most difficult mutant to cast was Ruby, who was a "touch of sweetness to the madness of the mutants."[2] Laura Ortiz was ultimately cast, making her film debut.

The Hills Have Eyes was a commercial success, playing in total 2,521 theaters and taking in its opening weekend $15,708,512.[3] The film grossed $41,778,863 in the United States Box Office[4] and $69,623,713 worldwide,[3] surpassing its budget costs by over fourfold.

The film placed third at the box office during its opening week.[5] It dropped to fifth after its second week of release, and to eighth after its third week. It fell out of the Top 10 into twelfth place after four weeks in release. After five weeks, it placed seventeenth at the box office, and it fell out of the Top 20 into twenty-first place after its sixth week. It continued to fall in subsequent weeks.[5]

The Hills Have Eyes was in first release for a total of 105 days, or 15 weeks, with its final showing on June 22, 2006.[3]

The movie got mixed reviews, with an average critic "Rotten" rating of 49% on Rotten Tomatoes and a critical consensus stating "Faster paced for today's audiences, this Hills remake ratchets up the gore for the hardcore horror fans, but will turn away casual audiences."[6]The Washington Post said: "this remake of the alleged 1977 Wes Craven classic has one very disturbing quality: It's too damned good."[7] Some have gone on to refer to the film as torture porn.[8]Bloody Disgusting, however, was scathing of those who referred to it as such, saying "some may call it “Torture porn” - these people are idiots".[9]Roger Ebert also gave a negative review, mentioning that the characters in the film are not familiar with horror movie, and went on to cite that the film should have focused more on the characters rather than the violence, saying "The Hills Have Eyes finds an intriguing setting in 'typical' fake towns built by the government [...] But its mutants are simply engines of destruction. There is a misshapen creature who coordinates attacks with a walkie-talkie; I would have liked to know more about him, but no luck."[10]